Prostate cancer is the leading incident cancer and the second leading cause of cancer deaths among men in the three major U.S. ethnic groups. However, those rates differ markedly among these groups. The racial differences in prostate cancer incidence and mortality could provide important clues to the etiology of the disease that could be exploited to further our understanding of prostate carcinogenesis. Prostate cancer is a model site for the study of the interplay of gene-environment interactions. In this proposed study, we will examine environmental factors in concert with genetic susceptibility in two ethnic groups with contrasting prostate cancer rates, African Americans and Mexican Americans, from a well-defined geographic area. We propose a population-based case-control study of genotypic, phenotypic, environmental and sociodemographic contributors to the etiology of prostate cancer in African Americans and Mexican Americans who are residents of the Houston area (Harris County, Texas). We will enroll 550 prostate cancer cases (200 Mexican Americans and 350 African Americans) and 750 controls (400 Mexican Americans and 350 African Americans) matched on age and race/ethnicity. Constitutional markers of genetic susceptibility and hormonal modulation, such as androgen receptor, 5-alpha-reductase type II, CYP17, CYP1B1, 3-beta-hydroxsteroid type II and vitamin D receptor, will be analyzed to determine if genotypic differences are associated with prostate cancer risk. Few studies have focused on minority populations, especially Hispanics, from a defined geographic area. Understanding how genetic predisposition and exogenous exposures interact to determine prostate cancer susceptibility will allow the development of more effective ethnic-specific prevention strategies.